This invention relates to new antiparasitic agents and in particular to a series of novel macrolide antibiotics related to the milbemycins and avermectins, and to processes for their preparation and compositions thereof.
The avermectins and milbemycins form an important group of broad spectrum antiparasitic agents possessing anthelmintic, ectoparasiticidal, insecticidal, antibacterial, antifungal and growth promoting activity with application in the areas of animal and human health, agriculture and horticulture. The avermectins, previously known as the C-076 compounds are produced by fermentation of a strain of the microorganism Streptomyces avermitilis ATCC 31267, 31271 or 31272 under aerobic conditions in an aqueous nutrient medium containing inorganic sales and assimilable sources of carbon and nitrogen. The production, isolation and chemical structure of the eight individual components which make up the C-076 complex is described in British patent specification 1573955. The milbemycins are structurally related macrolide antibiotics lacking the sugar residues at the 13-position. They are produced by fermentation, for example using Streptomyces hygroscopicus spp aureolacrimosus B-41-146 as described in British patent specification 1390336 or using Streptomyces cyaneogriseus spp noncyanogenus NRRL 15773 as described in EP-A-0170006 or using Streptomyces thermoarchaensis NCIB 12015 as described in British patent application GB 2166436.
In the search for new antibiotics, structural modification of known antibiotics is attempted whenever possible. This approach is limited, however, to modifications which retain the desired activity. Many antibiotics, including the avermectins and milbemycins, have such complex structures that many changes can be difficult to make by chemical means. The discovery of new antibiotics produced by fermentation processes continues, therefore, to be of great importance even in cases where the antibiotic, once recognized, is quite similar to a previously known antibiotic.
We have now discovered a group of novel macrolide antibiotics collectively designated herein as N787-182, which are produced by culture of a novel microorganism of the genus Streptomyces as described herein, together with certain related compounds prepared from the N787-182 compounds by simple chemical transformation processes. The compounds possess a broad spectrum of activity against insect pests, acari, free-living nematodes and endo- and ectoparasites afflicting animals and humans.